Topical application of enzymes has been described in the cosmetic as well as in the pharmaceutical field. For example, the use of proteases has been suggested to support or replace .alpha.-hydroxy acids in skin peeling preparations (Japanese patent application J04027388). Glutathion sulfhydryl oxidase has been identified as useful in hair-wave setting (Japanese patent application J04005220). Furthermore, International patent application WO93/19731 describes the use of glycosidases to enhance the process of skin desquamation and lysozyme has been mentioned to treat acne (HUT 057608). More recently, several patent applications using the enzyme transglutaminase have been published (WO94/18945, J02204407).
However, the limited storage stability of enzymes in liquid aqueous formulations is to be considered as the main limiting factor to the wider application of enzymes.
Commercial preparations containing enzymes often take advantage of the shelf stability of an enzyme in a dry state. According to such a concept, the easiest way to market an enzyme-containing product is by supplying the enzyme separately with the product, e.g. suitably packed as tablets. In an alternative approach, dry enzyme powder can be homogeneously dispersed into an essentially non-aqueous hydrophobic base, such as a suitable oil in combination with an oil gellant.
Disadvantage of the first approach is that the required dissolution of the enzyme tablet in an aqueous composition is slow and inconvenient. Regarding the second approach it should be noted that an enzyme requires water to be active. In order to be efficient, the mixing of an aqueous and an oily phase generally requires a relatively high energy input and cannot be achieved by simple hand-mixing. Thus, the mixing of an aqueous composition and a hydrophobic enzyme-containing phase is expected to be very inefficient.
The above problems can be circumvented by using aqueous stabilized enzyme compositions for topical applications. Unfortunately, aqueous enzyme formulations require high concentrations of water-miscible stabilizers intended to lower the water activity of the formulation. Polyols are often used for this purpose and long-term stability can only be effected by polyol concentrations well above 40% (v/v). However, enzymes often are not active in compositions containing high polyol concentrations. Especially the direct topical application of thus-stabilized enzyme composition will not provide sufficient water to reactivate the enzyme. Moreover, the presence of such high polyol concentrations in compositions for topical use is considered unacceptable.
Consequently, the high polyol concentration which is necessary to stabilize an enzyme in an aqueous environment prevents direct topical application of a thus-stabilized aqueous enzyme composition.
Another area in which enzymes can be advantageously used is the area of laundry hand wash applications. Although compared to machine washing the incidence of hand washing is very low in Europe and North America, hand washing remains popular as far as delicate fabrics are concerned. Of the delicate fabrics, the small category of woollen and silk items represents a particularly problematic area regarding stain removal, fabric depilling, colour revival and fabric shrinking. This category of specific fabrics may require specific enzymes, such as proteases active around a neutral pH value and/or at a low temperature or sulphur bridge rearranging enzymes like protein disulfide isomerase to counteract wool deformation stresses exerted during washing (EP 276547). A disadvantage of such niche products is that they obviously cannot bear the cost of extensive detergent or enzyme formulation developments.
Similarly, various biologically effective compounds other than enzymes are known which are unstable in aqueous end formulations, i.e. those formulations which are suitable for direct use in a specific application. Typically, biologically effective compounds like enzymes, antibiotics, vitamins, polyunsaturated compounds and the like, loose their activity upon prolonged storage in aqueous compositions. Although specific formulations are known in which said biologically effective compounds are stably incorporated, the latter formulations typically are not suitable for direct use in desired applications.